Bladder Defect Repair by Polycaprolactone/Gelatin Nanofiber Scaffolds Loaded with Mitomycin Through Anti-Fibrotic Effects

Congcong Yang,1,* Jianyou Xia,2,* Lunjie Zhao,3,* Jianping Tao,1,* Dan Li,1 Renxi Zhu,1 Qiang Wang,1 Haichen Shen,1 Baochao Zhang,4 Yujie Xu1 1Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China; 2Department of Urinary Surgery, General Hospital of Central Theater Command, Wuhan, 430012, People’s Republic of China; 3Department of Urology, Chinese People’s Armed Police Forces Anhui Provincial Corps Hospital, Hefei, 230001, People’s Republic of China; 4Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yujie Xu, Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China, Email [email protected] Baochao Zhang, Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, People’s Republic of China, Email [email protected]: In recent years, bladder defect repair has emerged as a critical issue in urological tissue engineering. Traditional treatment methods, such as autologous tissue transplantation and synthetic material repair, are limited by factors such as scarce donor sources, immune rejection, and postoperative fibrosis. Consequently, the development of nanofiber materials with bionic structures, biocompatibility, and anti-fibrotic capabilities has become a research hotspot. This research addressed the clinical needs associated with tuberculous bladder contracture, chronic cystitis, traumatic bladder rupture, and malignant tumors requiring partial cystectomy (such as localized non-muscle-invasive bladder cancer and urachal cancer), among other conditions. Excessive fibrotic scar formation following bladder surgery or injury is a primary contributor to reduced bladder compliance, diminished capacity, and impaired contractile function.Methods: Using electrospinning technology, we designed and prepared composite nanofibers with varying proportions (9:1, 7:3, 5:5) of polycaprolactone (PCL) and gelatin (GEL). By conducting various experiments such as scanning electron microscopy (SEM), water contact angle (WCA) analysis, mechanical performance evaluation, and Fourier transform infrared spectroscopy (FTIR), the PCL/GEL (7:3) composite material was ultimately selected as the one with the best overall performance.Results: Its fiber diameter was 612.14 ± 105.46 nm, water contact angle was 107.23°, and mechanical properties (tensile strength: 3.84 ± 0.5 MPa, elongation at break: 118.42 ± 4%, Young’s modulus: 19.50 ± 4.6 MPa). To enhance its anti-fibrotic properties, we incorporated mitomycin C (MMC) into the nanofiber matrix and prepared PCL/GEL/MMC nanofiber materials through blending and spinning. We then established a partial cystectomy model in rats, implanted the PCL/GEL/MMC nanofiber materials, and performed bladder imaging four weeks post-surgery to assess bladder capacity and morphological recovery. The CCK-8 assay was performed on days 1, 3, and 7, demonstrating that smooth muscle cells (SMCs) and endothelial cells (ECs) can effectively adhere, survive, and proliferate on these fibrous membranes, thereby confirming their biocompatibility. The anti-fibrotic properties of the materials were evaluated using immunofluorescence staining (IF)and immunohistochemical analysis (IHC).Conclusion: The experimental results demonstrated that PCL/GEL nanofiber materials loaded with 0.02% MMC exhibited excellent biocompatibility and anti-fibrotic effects in bladder defect repair, providing a theoretical basis for their potential clinical application.Keywords: bladder defect, electrospinning, mitomycin, anti-fibrotic therapy